Efficacy and Safety Study With Empagliflozin (BI 10773) vs. Placebo as add-on to Metformin or Metformin Plus Sulfonylurea Over 24 Weeks in Patients With Type 2 Diabetes

NCT01159600 | Completed Phase 3 Results

• 2 other identifiers: 1245.232009-016258-41
• Study Type: interventional
• Target: 1,504
• Locations: 11 countries
• Sites: 141

Brief Summary

The objective of the current study is to investigate the efficacy, safety and tolerability of two doses of BI 10773 compared to placebo given for 24 weeks as add-on therapy to metformin or metformin plus sulfonylurea in patients with Typ 2 Diabetes Mellitus with insufficient glycaemic control.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• HbA1c Change From Baseline

  Change from baseline in HbA1c after 24 weeks. For open-label groups the descriptive mean is provided, for randomised groups adjusted means are provided. The means are adjusted separately for metformin alone and metformin plus sulphonylurea background medication.

  Baseline and 24 weeks

Secondary Outcomes (2)

• Body Weight Change From Baseline

  Baseline and 24 weeks

• Mean Daily Plasma Glucose (MDG) Change From Baseline

  Baseline and 24 weeks

Other Outcomes (1)

• Confirmed Hypoglycaemic Adverse Events

  From first intake of randomised trial medication until 7 days after last trial medication intake, up to 231 days

Study Arms (4)

BI 10773 Arm 2

EXPERIMENTAL

BI 10773 once daily high dose

Drug: BI 10773; Drug: Placebo identical to BI 10773 low dose

Placebo

PLACEBO COMPARATOR

Placebo matching BI 10773

Drug: Placebo identical to BI 10773 low dose; Drug: Placebo identical to BI 10773 high dose

BI 10773 open-label

EXPERIMENTAL

BI 10773 once daily high dose open label

Drug: BI 10773

BI 10773 Arm 1

EXPERIMENTAL

BI 10773 once daily low dose

Drug: Placebo identical to BI 10773 high dose; Drug: BI 10773

Interventions

Placebo identical to BI 10773 high dose DRUG

Placebo tablets matching BI 10773 high dose

BI 10773 Arm 1

Placebo identical to BI 10773 low dose DRUG

Placebo tablets matching BI 10773 low dose

Placebo

BI 10773 DRUG

BI 10773 tablets once daily high dose open label

BI 10773 open-label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of type 2 diabetes mellitus prior to informed consent
• Male and female patients on a diet and exercise regimen who are pre-treated with immediate release metformin or immediate release metformin plus sulfonylurea (see below for minimum doses). The treatment regimen has to be unchanged for 12 weeks prior to randomisation.
• Minimum dose for metformin: \> or = 1500 mg/day or maximum tolerated dose or maximum dose according to local label Minimum dose for sulfonylurea: \> or = half of the maximal recommended dose or maximum tolerated dose or maximum dose according to local label
• HbA1c of \> or = 7.0% and \< or = 11% at Visit 1 (screening) in order to be eligible for randomised treatment HbA1c of \> 11% at Visit 1 (screening) in order to be eligible for the open-label treatment arm (25 mg BI 10773)
• Age\> or = 18
• Body Mass Index (BM)I \< or = 45 kg/m2 (Body Mass Index) at Visit 1 (Screening)
• Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation

You may not qualify if:

• Uncontrolled hyperglycaemia with a glucose level \> 240 mg/dl (\>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day)
• Myocardial infarction, stroke or transient ischemic attack (TIA) within 3 months prior to informed consent
• Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during screening and/or run-in phase
• Impaired renal function, defined as eGFR\<30 ml/min (severe renal impairment) as determined during screening and/or run-in phase
• Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption
• Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
• Contraindications to metformin and/or sulfonylurea according to the local label for those patients that enter the study with the respective background therapy
• Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anaemia)
• Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to informed consent or any other treatment at the time of screening (i.e. surgery, aggressive diet regimen, etc.) leading to unstable body weight
• Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except Typ 2 Diabetes
• Pre-menopausal women (last menstruation ¿ 1 year prior to informed consent) who:
• are nursing or pregnant or
• are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence (if acceptable by local authorities), double barrier method and vasectomised partner
• Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake
• Participation in another trial with an investigational drug within 30 days prior to informed consent

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Eli Lilly and Company: collaborator

Study Sites (148)

1245.23.10145 Boehringer Ingelheim Investigational Site

Birmingham, Alabama, United States

Location

1245.23.10046 Boehringer Ingelheim Investigational Site

Tempe, Arizona, United States

Location

1245.23.10095 Boehringer Ingelheim Investigational Site

Huntington Park, California, United States

Location

1245.23.10109 Boehringer Ingelheim Investigational Site

Huntington Park, California, United States

Location

1245.23.10074 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

Location

1245.23.10149 Boehringer Ingelheim Investigational Site

Rancho Cucamonga, California, United States

Location

1245.23.10127 Boehringer Ingelheim Investigational Site

Waterbury, Connecticut, United States

Location

1245.23.10042 Boehringer Ingelheim Investigational Site

Fort Lauderdale, Florida, United States

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1245.23.10133 Boehringer Ingelheim Investigational Site

Jupiter, Florida, United States

Location

1245.23.10080 Boehringer Ingelheim Investigational Site

Decatur, Georgia, United States

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1245.23.10001 Boehringer Ingelheim Investigational Site

Chicago, Illinois, United States

Location

1245.23.10159 Boehringer Ingelheim Investigational Site

Des Moines, Iowa, United States

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1245.23.10117 Boehringer Ingelheim Investigational Site

Arkansas City, Kansas, United States

Location

1245.23.10157 Boehringer Ingelheim Investigational Site

Newton, Kansas, United States

Location

1245.23.10148 Boehringer Ingelheim Investigational Site

Lexington, Kentucky, United States

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1245.23.10034 Boehringer Ingelheim Investigational Site

Rochester, New York, United States

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1245.23.10123 Boehringer Ingelheim Investigational Site

Smithtown, New York, United States

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1245.23.10120 Boehringer Ingelheim Investigational Site

Columbus, Ohio, United States

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1245.23.10031 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

Location

1245.23.10158 Boehringer Ingelheim Investigational Site

Mt. Pleasant, South Carolina, United States

Location

1245.23.10015 Boehringer Ingelheim Investigational Site

Simpsonville, South Carolina, United States

Location

1245.23.10156 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Location

1245.23.10153 Boehringer Ingelheim Investigational Site

Hurst, Texas, United States

Location

1245.23.10143 Boehringer Ingelheim Investigational Site

Killeen, Texas, United States

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1245.23.10106 Boehringer Ingelheim Investigational Site

San Antonio, Texas, United States

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1245.23.20032 Boehringer Ingelheim Investigational Site

Calgary, Alberta, Canada

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1245.23.20023 Boehringer Ingelheim Investigational Site

Edmonton, Alberta, Canada

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1245.23.20028 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

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1245.23.20033 Boehringer Ingelheim Investigational Site

Victoria, British Columbia, Canada

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1245.23.20024 Boehringer Ingelheim Investigational Site

Paradise, Newfoundland and Labrador, Canada

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1245.23.20031 Boehringer Ingelheim Investigational Site

St. John's, Newfoundland and Labrador, Canada

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1245.23.20026 Boehringer Ingelheim Investigational Site

Halifax, Nova Scotia, Canada

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1245.23.20001 Boehringer Ingelheim Investigational Site

Barrie, Ontario, Canada

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1245.23.20022 Boehringer Ingelheim Investigational Site

Brampton, Ontario, Canada

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1245.23.20035 Boehringer Ingelheim Investigational Site

Corunna, Ontario, Canada

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1245.23.20030 Boehringer Ingelheim Investigational Site

Etobicoke, Ontario, Canada

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1245.23.20037 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

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1245.23.20029 Boehringer Ingelheim Investigational Site

London, Ontario, Canada

Location

1245.23.20003 Boehringer Ingelheim Investigational Site

Markham, Ontario, Canada

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1245.23.20040 Boehringer Ingelheim Investigational Site

Oakville, Ontario, Canada

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1245.23.20034 Boehringer Ingelheim Investigational Site

Sarnia, Ontario, Canada

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1245.23.20039 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

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1245.23.20027 Boehringer Ingelheim Investigational Site

Laval, Quebec, Canada

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1245.23.20025 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

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1245.23.20038 Boehringer Ingelheim Investigational Site

Saint-Laurent, Quebec, Canada

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1245.23.20036 Boehringer Ingelheim Investigational Site

Sherbrooke, Quebec, Canada

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1245.23.86031 Boehringer Ingelheim Investigational Site

Beijing, China

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1245.23.86032 Boehringer Ingelheim Investigational Site

Beijing, China

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1245.23.86033 Boehringer Ingelheim Investigational Site

Beijing, China

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1245.23.86034 Boehringer Ingelheim Investigational Site

Beijing, China

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1245.23.86035 Boehringer Ingelheim Investigational Site

Beijing, China

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1245.23.86048 Boehringer Ingelheim Investigational Site

Chengdu, China

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1245.23.86058 Boehringer Ingelheim Investigational Site

Chongqing, China

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1245.23.86038 Boehringer Ingelheim Investigational Site

Dalian, China

Location

1245.23.86002 Boehringer Ingelheim Investigational Site

Guangzhou, China

Location

1245.23.86052 Boehringer Ingelheim Investigational Site

Guangzhou, China

Location

1245.23.86037 Boehringer Ingelheim Investigational Site

Haerbin, China

Location

1245.23.86049 Boehringer Ingelheim Investigational Site

Jinan, China

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1245.23.86053 Boehringer Ingelheim Investigational Site

Jinan, China

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1245.23.86042 Boehringer Ingelheim Investigational Site

Nanjing, China

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1245.23.86043 Boehringer Ingelheim Investigational Site

Nanjing, China

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1245.23.86055 Boehringer Ingelheim Investigational Site

Nanning, China

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1245.23.86056 Boehringer Ingelheim Investigational Site

Nanning, China

Location

1245.23.86039 Boehringer Ingelheim Investigational Site

Shanghai, China

Location

1245.23.86040 Boehringer Ingelheim Investigational Site

Shanghai, China

Location

1245.23.86054 Boehringer Ingelheim Investigational Site

Shantou, China

Location

1245.23.86057 Boehringer Ingelheim Investigational Site

Shenyang, China

Location

1245.23.86045 Boehringer Ingelheim Investigational Site

Shijiazhuang, China

Location

1245.23.86013 Boehringer Ingelheim Investigational Site

Suzhou, China

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1245.23.86036 Boehringer Ingelheim Investigational Site

Tianjin, China

Location

1245.23.86041 Boehringer Ingelheim Investigational Site

Xi'an, China

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1245.23.86051 Boehringer Ingelheim Investigational Site

Zhenjiang, China

Location

1245.23.33015 Boehringer Ingelheim Investigational Site

Arras, France

Location

1245.23.33008 Boehringer Ingelheim Investigational Site

Bersée, France

Location

1245.23.33020 Boehringer Ingelheim Investigational Site

Bischheim, France

Location

1245.23.33002 Boehringer Ingelheim Investigational Site

Bondy, France

Location

1245.23.33016 Boehringer Ingelheim Investigational Site

Bruay-la-Buissière, France

Location

1245.23.33001 Boehringer Ingelheim Investigational Site

Corbeil-Essonnes, France

Location

1245.23.33010 Boehringer Ingelheim Investigational Site

Croix, France

Location

1245.23.33009 Boehringer Ingelheim Investigational Site

Hautmont, France

Location

1245.23.33003 Boehringer Ingelheim Investigational Site

La Rochelle, France

Location

1245.23.33045 Boehringer Ingelheim Investigational Site

Marseille, France

Location

1245.23.33014 Boehringer Ingelheim Investigational Site

Mundolsheim, France

Location

1245.23.33004 Boehringer Ingelheim Investigational Site

Narbonne, France

Location

1245.23.33012 Boehringer Ingelheim Investigational Site

Schiltigheim, France

Location

1245.23.33013 Boehringer Ingelheim Investigational Site

Strasbourg, France

Location

1245.23.33019 Boehringer Ingelheim Investigational Site

Strasbourg, France

Location

1245.23.33007 Boehringer Ingelheim Investigational Site

Vieux-Condé, France

Location

1245.23.33018 Boehringer Ingelheim Investigational Site

Wattrelos, France

Location

1245.23.49001 Boehringer Ingelheim Investigational Site

Dormagen, Germany

Location

1245.23.49009 Boehringer Ingelheim Investigational Site

Flörsheim, Germany

Location

1245.23.49004 Boehringer Ingelheim Investigational Site

Hatten, Germany

Location

1245.23.49007 Boehringer Ingelheim Investigational Site

Künzing, Germany

Location

1245.23.49002 Boehringer Ingelheim Investigational Site

Neuwied, Germany

Location

1245.23.49008 Boehringer Ingelheim Investigational Site

Nuremberg, Germany

Location

1245.23.49010 Boehringer Ingelheim Investigational Site

Rednitzhembach, Germany

Location

1245.23.49006 Boehringer Ingelheim Investigational Site

Rehburg-Loccum, Germany

Location

1245.23.49011 Boehringer Ingelheim Investigational Site

Rehlingen-Siersburg, Germany

Location

1245.23.49005 Boehringer Ingelheim Investigational Site

Saarbrücken, Germany

Location

1245.23.49003 Boehringer Ingelheim Investigational Site

Unterschneidheim, Germany

Location

1245.23.91101 Boehringer Ingelheim Investigational Site

Coimbatore, India

Location

1245.23.91104 Boehringer Ingelheim Investigational Site

Indore, India

Location

1245.23.91103 Boehringer Ingelheim Investigational Site

Maharashtra, India

Location

1245.23.91102 Boehringer Ingelheim Investigational Site

Nagpur, India

Location

1245.23.91105 Boehringer Ingelheim Investigational Site

Pune, India

Location

1245.23.52003 Boehringer Ingelheim Investigational Site

Guadalajara, Mexico

Location

1245.23.52004 Boehringer Ingelheim Investigational Site

Guadalajara, Mexico

Location

1245.23.52001 Boehringer Ingelheim Investigational Site

Monterrey, Mexico

Location

1245.23.52002 Boehringer Ingelheim Investigational Site

Monterrey, Mexico

Location

1245.23.74005 Boehringer Ingelheim Investigational Site

Bratislava, Slovakia

Location

1245.23.74002 Boehringer Ingelheim Investigational Site

Lučenec, Slovakia

Location

1245.23.74006 Boehringer Ingelheim Investigational Site

Nitra, Slovakia

Location

1245.23.74014 Boehringer Ingelheim Investigational Site

Nové Zámky, Slovakia

Location

1245.23.74001 Boehringer Ingelheim Investigational Site

Považská Bystrica, Slovakia

Location

1245.23.74004 Boehringer Ingelheim Investigational Site

Prešov, Slovakia

Location

1245.23.74003 Boehringer Ingelheim Investigational Site

Trebišov, Slovakia

Location

1245.23.38003 Boehringer Ingelheim Investigational Site

Celje, Slovenia

Location

1245.23.38002 Boehringer Ingelheim Investigational Site

Koper, Slovenia

Location

1245.23.38001 Boehringer Ingelheim Investigational Site

Maribor, Slovenia

Location

1245.23.82012 Boehringer Ingelheim Investigational Site

Anyang, South Korea

Location

1245.23.82004 Boehringer Ingelheim Investigational Site

Busan, South Korea

Location

1245.23.82011 Boehringer Ingelheim Investigational Site

Goyang, South Korea

Location

1245.23.82009 Boehringer Ingelheim Investigational Site

Ilsan, South Korea

Location

1245.23.82001 Boehringer Ingelheim Investigational Site

Incheon, South Korea

Location

1245.23.82006 Boehringer Ingelheim Investigational Site

Jeonju, South Korea

Location

1245.23.82005 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1245.23.82007 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1245.23.82008 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1245.23.82010 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1245.23.82014 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1245.23.82002 Boehringer Ingelheim Investigational Site

Suwon, South Korea

Location

1245.23.82003 Boehringer Ingelheim Investigational Site

Wŏnju, South Korea

Location

1245.23.88010 Boehringer Ingelheim Investigational Site

Kaohsiung City, Taiwan

Location

1245.23.88011 Boehringer Ingelheim Investigational Site

Kaohsiung City, Taiwan

Location

1245.23.88012 Boehringer Ingelheim Investigational Site

Kaohsiung City, Taiwan

Location

1245.23.88013 Boehringer Ingelheim Investigational Site

Kaohsiung City, Taiwan

Location

1245.23.88009 Boehringer Ingelheim Investigational Site

Taichung, Taiwan

Location

1245.23.88014 Boehringer Ingelheim Investigational Site

Tainan, Taiwan

Location

1245.23.88006 Boehringer Ingelheim Investigational Site

Taipei, Taiwan

Location

1245.23.88007 Boehringer Ingelheim Investigational Site

Taipei, Taiwan

Location

1245.23.88021 Boehringer Ingelheim Investigational Site

Taipei, Taiwan

Location

1245.23.88008 Boehringer Ingelheim Investigational Site

Taoyuan, Taiwan

Location

1245.23.90003 Boehringer Ingelheim Investigational Site

Erzurum, Turkey (Türkiye)

Location

1245.23.90001 Boehringer Ingelheim Investigational Site

Gaziantep, Turkey (Türkiye)

Location

1245.23.90002 Boehringer Ingelheim Investigational Site

Istanbul, Turkey (Türkiye)

Location

1245.23.90006 Boehringer Ingelheim Investigational Site

Istanbul, Turkey (Türkiye)

Location

1245.23.90007 Boehringer Ingelheim Investigational Site

Istanbul, Turkey (Türkiye)

Location

1245.23.90004 Boehringer Ingelheim Investigational Site

Izmir, Turkey (Türkiye)

Location

Related Publications (5)

• Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

  PMID: 38770818 DERIVED

• Tuttle KR, Levin A, Nangaku M, Kadowaki T, Agarwal R, Hauske SJ, Elsasser A, Ritter I, Steubl D, Wanner C, Wheeler DC. Safety of Empagliflozin in Patients With Type 2 Diabetes and Chronic Kidney Disease: Pooled Analysis of Placebo-Controlled Clinical Trials. Diabetes Care. 2022 Jun 2;45(6):1445-1452. doi: 10.2337/dc21-2034.

  PMID: 35472672 DERIVED

• Inzucchi SE, Davies MJ, Khunti K, Trivedi P, George JT, Zwiener I, Johansen OE, Sattar N. Empagliflozin treatment effects across categories of baseline HbA1c, body weight and blood pressure as an add-on to metformin in patients with type 2 diabetes. Diabetes Obes Metab. 2021 Feb;23(2):425-433. doi: 10.1111/dom.14234. Epub 2020 Nov 20.

  PMID: 33084149 DERIVED

• Cherney D, Lund SS, Perkins BA, Groop PH, Cooper ME, Kaspers S, Pfarr E, Woerle HJ, von Eynatten M. The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia. 2016 Sep;59(9):1860-70. doi: 10.1007/s00125-016-4008-2. Epub 2016 Jun 17.

  PMID: 27316632 DERIVED

• Haring HU, Merker L, Seewaldt-Becker E, Weimer M, Meinicke T, Woerle HJ, Broedl UC; EMPA-REG METSU Trial Investigators. Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2013 Nov;36(11):3396-404. doi: 10.2337/dc12-2673. Epub 2013 Aug 20.

  PMID: 23963895 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2010
• First Posted: July 9, 2010
• Study Start: July 1, 2010
• Primary Completion: February 1, 2012
• Last Updated: June 17, 2014
• Results First Posted: June 17, 2014

Record last verified: 2014-05

Locations

US (25); DE (11); TU (6); ME (4); CA (21); KR (13); CN (26); FR (17); IN (5); SL (3); TW (10)